Tumor-associated macrophages exhibit pro- and anti-inflammatory properties by which they impact on pancreatic tumorigenesis
Tumor-associated macrophages exhibit pro- and anti-inflammatory properties by which they impact on pancreatic tumorigenesis
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DOI：
10.1002/ijc.28736
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发表时间：
2014-08-15
影响因子：
6.4
通讯作者：
Sebens, Susanne
中科院分区：
文献类型：
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作者：
Helm, Ole;Held-Feindt, Janka;Sebens, Susanne
胰腺导管腺癌（PDAC）仍然在致死性肿瘤疾病中排名第4，其特征在于具有大量肿瘤相关巨噬细胞（TAM）的深层肿瘤基质。在环境因素的驱动下，单核细胞分化为M1-或M2-巨噬细胞，后者通常被认为是促肿瘤的。由于仍然缺乏TAM在人PDAC发育中的详细分析，因此分析了新鲜分离的PDAC衍生的TAM的表型和对良性（H6 c7）和恶性（Colo 357）胰腺导管上皮细胞的上皮-间充质转化（EMT）的影响。TAM表现出M1-巨噬细胞（表达HLA-DR、IL-1 β或TNF-α）和M2-巨噬细胞（表达CD 163和IL-10）的特征。在TAM的存在下，H6 c7和Colo 357细胞显示出伸长的细胞形状沿着，同时间充质标志物如波形蛋白的表达增加和上皮E-钙粘蛋白的表达减少。与TAM类似，体外产生的M1-和M2-巨噬细胞在H6 c7和Colo 357细胞中均介导EMT。M1-巨噬细胞在共培养期间获得M2-特征，这可以通过GM-CSF处理来防止。然而，M1-巨噬细胞在H6 c7和Colo 357细胞中仍然有效地诱导EMT，尽管缺乏M2-特征。总体而言，这些数据表明TAM表现出抗炎和促炎特性，这些特性同样有助于PDAC起始和发展中的EMT诱导。
Pancreatic ductal adenocarcinoma (PDAC) still ranking 4th in the order of fatal tumor diseases is characterized by a profound tumor stroma with high numbers of tumor-associated macrophages (TAMs). Driven by environmental factors, monocytes differentiate into M1- or M2-macrophages, the latter commonly regarded as being protumorigenic. Because a detailed analysis of TAMs in human PDAC development is still lacking, freshly isolated PDAC-derived TAMs were analyzed for their phenotype and impact on epithelial-mesenchymal-transition (EMT) of benign (H6c7) and malignant (Colo357) pancreatic ductal epithelial cells. TAMs exhibited characteristics of M1-macrophages (expression of HLA-DR, IL-1 beta, or TNF-alpha) and M2-macrophages (expression of CD163 and IL-10). In the presence of TAMs, H6c7, and Colo357 cells showed an elongated cell shape along with an increased expression of mesenchymal markers such as vimentin and reduced expression of epithelial E-cadherin. Similar to TAMs, in vitro generated M1- and M2-macrophages both mediated EMT in H6c7 and Colo357 cells. M1-macrophages acquired M2-characteristics during coculture that could be prevented by GM-CSF treatment. However, M1-macrophages still potently induced EMT in H6c7 and Colo357 cells although lacking M2-characteristics. Overall, these data demonstrate that TAMs exhibit anti-as well as proinflammatory properties that equally contribute to EMT induction in PDAC initiation and development.